MST1R

macrophage stimulating 1 receptor, the group of CD molecules|IPT domain containing|Receptor tyrosine kinases

Basic information

Region (hg38): 3:49887001-49903873

Previous symbols: [ "RON", "PTK8", "SEA" ]

Links

ENSG00000164078 ∙ NCBI:4486 ∙ OMIM:600168 ∙ HGNC:7381 ∙ Uniprot:Q04912 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• nasopharyngeal carcinoma, susceptibility to, 3 (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MST1R gene.

• Inborn genetic diseases (50 variants)
• not provided (15 variants)
• not specified (1 variants)
• Nasopharyngeal carcinoma, susceptibility to, 3 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MST1R gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	4	6
missense			47	5	5	57
nonsense				2		2
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	47	9	9

Variants in MST1R

This is a list of pathogenic ClinVar variants found in the MST1R region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-49887339-G-A		not specified	Uncertain significance (Sep 27, 2021)
3-49887356-C-A		MST1R-related disorder • not specified	Conflicting classifications of pathogenicity (Jul 14, 2021)
3-49887369-A-G		not specified	Likely benign (Feb 28, 2023)
3-49887381-G-A			Uncertain significance (-)
3-49887468-G-T		not specified	Uncertain significance (Mar 02, 2023)
3-49887507-T-C		MST1R-related disorder	Benign (Oct 21, 2019)
3-49887514-G-A			Benign (Dec 31, 2019)
3-49889957-C-T		not specified	Uncertain significance (Aug 04, 2023)
3-49889961-G-A		not specified	Uncertain significance (Mar 07, 2023)
3-49890070-G-T		MST1R-related disorder	Benign (Dec 16, 2019)
3-49890531-G-A		not specified	Uncertain significance (Dec 07, 2021)
3-49890546-G-A		not specified	Uncertain significance (Apr 11, 2023)
3-49890552-C-T		not specified	Uncertain significance (Aug 08, 2022)
3-49890576-C-G		not specified	Uncertain significance (Oct 06, 2023)
3-49890601-C-T		not specified	Uncertain significance (Apr 10, 2023)
3-49890602-G-A			Benign (Dec 31, 2019)
3-49890603-C-T		not specified	Uncertain significance (Jan 31, 2024)
3-49891261-G-A		not specified	Uncertain significance (Jan 26, 2022)
3-49891263-G-A		not specified	Uncertain significance (Aug 02, 2021)
3-49891401-G-A		not specified	Uncertain significance (Oct 12, 2021)
3-49891412-C-T		not specified	Uncertain significance (Aug 16, 2021)
3-49891421-T-C		not specified	Uncertain significance (Dec 20, 2023)
3-49891445-T-C		not specified	Uncertain significance (Jan 26, 2022)
3-49891485-T-C		not specified	Likely benign (Feb 17, 2024)
3-49891557-C-T		not specified	Uncertain significance (Dec 11, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MST1R	protein_coding	protein_coding	ENST00000296474	20	16865

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.87e-37	0.00000480	124993	3	752	125748	0.00301

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.682	796	852	0.934	0.0000547	8943
Missense in Polyphen		268	296.26	0.90461		3292
Synonymous	1.41	326	360	0.905	0.0000229	3080
Loss of Function	-0.0592	55	54.5	1.01	0.00000297	578

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0211	0.0209
Ashkenazi Jewish	0.00218	0.00218
East Asian	0.00152	0.00152
Finnish	0.00226	0.00222
European (Non-Finnish)	0.00196	0.00195
Middle Eastern	0.00152	0.00152
South Asian	0.00177	0.00173
Other	0.000816	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to MST1 ligand. Regulates many physiological processes including cell survival, migration and differentiation. Ligand binding at the cell surface induces autophosphorylation of RON on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1 or the adapter GAB1. Recruitment of these downstream effectors by RON leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. RON signaling activates the wound healing response by promoting epithelial cell migration, proliferation as well as survival at the wound site. Plays also a role in the innate immune response by regulating the migration and phagocytic activity of macrophages. Alternatively, RON can also promote signals such as cell migration and proliferation in response to growth factors other than MST1 ligand. {ECO:0000269|PubMed:18836480, ECO:0000269|PubMed:7939629, ECO:0000269|PubMed:9764835}.
• Disease: DISEASE: Nasopharyngeal carcinoma, 3 (NPCA3) [MIM:617075]: A form of nasopharyngeal carcinoma, a malignant neoplasm that originates in the nasopharyngeal epithelium and includes 4 subtypes: keratinizing squamous cell, non-keratinizing, basaloid squamous cell, and papillary adenocarcinoma. {ECO:0000269|PubMed:26951679}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: Signal Transduction;Alpha6Beta4Integrin;a6b1 and a6b4 Integrin signaling;Signaling by MST1;Signaling by Receptor Tyrosine Kinases;amb2 Integrin signaling (Consensus)

Recessive Scores

• pRec: 0.154

Intolerance Scores

• loftool: 0.857
• rvis_EVS: -1.78
• rvis_percentile_EVS: 2.29

Haploinsufficiency Scores

• pHI: 0.326
• hipred: N
• hipred_score: 0.352
• ghis: 0.513

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.749

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Mst1r
• Phenotype: immune system phenotype; liver/biliary system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; hematopoietic system phenotype; endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: mst1rb
• Affected structure: bone mineralization
• Phenotype tag: abnormal
• Phenotype quality: delayed

Gene ontology

• Biological process: defense response;signal transduction;transmembrane receptor protein tyrosine kinase signaling pathway;single fertilization;positive regulation of cell population proliferation;response to virus;Wnt signaling pathway;peptidyl-tyrosine phosphorylation;macrophage colony-stimulating factor signaling pathway;positive regulation of MAP kinase activity;innate immune response;hepatocyte growth factor receptor signaling pathway;positive regulation of protein kinase B signaling
• Cellular component: stress fiber;vacuole;plasma membrane;integral component of plasma membrane;cell surface;receptor complex
• Molecular function: transmembrane receptor protein tyrosine kinase activity;macrophage colony-stimulating factor receptor activity;protein binding;ATP binding;Wnt-protein binding;enzyme binding